Gfa. Kersten et al., SINGLE-SHOT WITH TETANUS TOXOID IN BIODEGRADABLE MICROSPHERES PROTECTS MICE DESPITE ACID-INDUCED DENATURATION OF THE ANTIGEN, Vaccine, 14(17-18), 1996, pp. 1627-1632
Tetanus toroid encapsulated in microspheres consisting of biodegradabl
e polyesters, prepared by four different manufacturers were evaluated
with respect to antigenic load, in vitro release pattern, antigen inte
grity and immunogenicity. In vitro release studies over periods up to
140 days indicated that only during the first days tetanus toroid was
released. Although some preparations were designed to release their an
tigen content in a pulsatile manner, this was never observed in vitro.
A single immunization with 0.3 Lf tetanus toroid in microspheres indu
ced substantial humoral responses, in most cases higher than one immun
ization with plain tetanus toroid, sometimes higher than one dose of a
lum-adsorbed toroid but always lower than booster immunizations. It is
shown that the moderate (no booster effect) performance of the micros
phere preparations is probably due to acid induced denaturation of the
antigen. Despite this drawback, protection level in mice after challe
nge with 50 LD(50) 1 year after one immunization with microspheres was
, on average, substantially higher than mice receiving plain tetanus t
oroid. Copyright (C) 1996 Elsevier Science Ltd.